This project's aims: 1. To achieve an improved total synthesis of pumiliotoxin C and a series of pumiliotoxin C R2 side-chain analogs. 2. To achieve a total synthesis of pumiliotoxins II and III and pumiliotoxin carbocyclic ring analogs. 3. To achieve a total synthesis of gephyrotoxin and dihydrogephyrotoxin. 4. To collaborate in the detailed pharmacological evaluation of the neurological activity of the synthetic pumiliotoxins, gephyrotoxins, and toxin analogs. 5. To explore the utility of 2-axonia-(3,3)-sigmatropic rearrangements for carbon-carbon bond formation. To apply this methodology to the elaboration of the gephyrotoxin C ring. 6. To achieve a total synthesis of pretazettine. 7. To prepare a series of pretazettine C-8 analogs and collaborate in their pharmacological evaluation.